N. gonorrhoeae remains a common and severe STD. A variety of outer membrane structures believed to be critical to the pathogenicity of the organism have been identified, and mutant organisms have been generated. However, no valid animal model of gonococcal disease is available, and the correlation between in vitro tissue culture infection and human disease are not known. More than 20 years ago Kellogg used a human challenge model to conduct seminal experiments demonstrating the importance of pili in infection. Human challenge studies have been conducted by other investigators without reported sequelae. Most recently Swanson and coworkers used this model to demonstrate the importance of selective pressure in vivo on PII (opa) proteins and pili. We wish to establish a Center for human challenge studies to be used as a national resource, and for vaccine development. In these studies we plan to examine whether the following characteristics are required for infection: 1) PIIs expressed under selective pressure; 2) a 36 Kd adhesion; 3) iron transport proteins; 4) L(+)-lactate dehydrogenase. Significant literature support the potential importance of each of these variables. We believe human challenge studies for gonorrhoeae will provide information essential to vaccine development. We believe UNC to be an ideal institution for development of this Center because of long- standing collaboration between clinical investigators and basic researchers interested in gonococcal disease, and because of a well established Clinical Research Unit in which these studies can be conducted in an economical fashion.